Phase 1 Study of Vorinostat and Bortezomib in Multiple Myeloma (MK-0683-015 EXT 1 (AM1))

A Phase 1 study testing vorinostat and bortezomib in people with Multiple Myeloma, run by Merck Sharp & Dohme LLC.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial summary

The purposes of this study are: To determine the maximum tolerated dose (MTD) for the combination of oral vorinostat and bortezomib in participants with advanced multiple myeloma To assess the safety and tolerability of this regimen and to document the participant's clinical status (by anti-tumor activity) for this… Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Multiple Myeloma
What is being tested?: vorinostat and bortezomib
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 34 participants
Where: No sites listed yet
Study dates: Sep 2005to May 2011
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Adults with refractory or relapsed multiple myeloma
Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 (a measurement to determine participant's ability to perform daily activities)
Adequate bone marrow reserve
Adequate hepatic and renal function
Ability to swallow capsules
3 weeks or more since prior chemotherapy and have recovered from prior toxicities

Who cannot join

Participants who plan to have a bone marrow transplant within 4 weeks of start of treatment
Participants with prior treatment with other investigational agents with a similar anti-tumor mechanism
Participants with other active/uncontrolled clinically significant illness
Pregnant or nursing female participants
Participants who received bortezomib within 3 months of start of this trial

About this study

Official title: Phase I Clinical Trial of Vorinostat (MK-0683) in Combination With Bortezomib in Patients With Advanced Multiple Myeloma

The purposes of this study are:

To determine the maximum tolerated dose (MTD) for the combination of oral vorinostat and bortezomib in participants with advanced multiple myeloma
To assess the safety and tolerability of this regimen and to document the participant's clinical status (by anti-tumor activity) for this combination, as determined per standard of care.

Conditions: Multiple Myeloma
Being tested: vorinostat, bortezomib
Medical subject headings: Multiple Myeloma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

vorinostatDrug
Also called MK0683, Zolinza®, Suberoylanilide Hydroxamic Acid (SAHA)
Vorinostat capsules. Treatment in 21 day cycles (participants receive vorinostat for 14 days followed by a 7 day break).
bortezomibDrug
Also called Velcade
Bortezomib injection. Given twice weekly for 2 weeks with a 1 week break. Treatment in 21 day cycles.

Study groups in NCT00111813
Study group	Role	What they receive
vorinostat 200 mg + bortezomib 0.7 mg/m^2	Experimental	Vorinostat capsules given twice daily (b.i.d.); bortezomib injection given on Days 4, 8, 11, and 15 of each cycle. Receives: Drug: vorinostat; Drug: bortezomib
vorinostat 200 mg + bortezomib 0.9 mg/m^2	Experimental	Vorinostat capsules given b.i.d.; bortezomib injection given on Days 4, 8, 11, and 15 of each cycle. Receives: Drug: vorinostat; Drug: bortezomib
vorinostat 300 mg + bortezomib 1.3 mg/m^2	Experimental	Vorinostat given once daily (q.d.); bortezomib given on Days 1, 4, 8, and 11 of each cycle. Receives: Drug: vorinostat; Drug: bortezomib
vorinostat 400 mg + bortezomib 0.9 mg/m^2	Experimental	Vorinostat given q.d.; bortezomib given on Days 1, 4, 8, and 11 of each cycle. Receives: Drug: vorinostat; Drug: bortezomib
vorinostat 400 mg + bortezomib 1.1 mg/m^2	Experimental	Vorinostat given q.d.; bortezomib given on Days 1, 4, 8, and 11 of each cycle. Receives: Drug: vorinostat; Drug: bortezomib
vorinostat 400 mg + bortezomib 1.3 mg/m^2	Experimental	Vorinostat given q.d.; bortezomib given on Days 1, 4, 8, and 11 of each cycle. Receives: Drug: vorinostat; Drug: bortezomib

What is being measured

The primary outcome is the main question the study is designed to answer.

Mean Duration of Treatment With Vorinostat
Event causing discontinuation from the study was defined as (1) progressive disease OR (2) intolerable toxicity.
Progressive disease was defined as:
- >25% increase in the level of serum monoclonal paraprotein.
- 25% increase in 24-hour urinary light chain excretion.
- >25% increase in plasma cells in a bone marrow aspirate or on trephine biopsy.
- Development of new bone lesions or soft tissue plasmacytomas.
- Development of hypercalcemia.
Intolerable toxicity was based on the clinical judgment of the investigator.
Measured: Day 1 to an event causing discontinuation from the study, assessed up to 29 months

Secondary outcomes (4)

Number of Participants With Dose Modifications of Either Vorinostat or Bortezomib Due to Adverse Experiences (AEs) After Treatment With Study Drug
An adverse experience (AE) was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the sponsor's product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which was temporally associated with the use of the sponsor's product, was also an adverse experience.
Measured: Day 1 to disease progression, toxicity, or death, assessed up to 29 months
Mean Time to First AE Resulting in a Dose Modification in Either Vorinostat or Bortezomib
An AE was defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the sponsor's product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which was temporally associated with the use of the sponsor's product, was also an adverse experience.
Measured: Day 1 to disease progression, toxicity, or death, assessed up to 29 months
Clinical AE Summary
An AE was defined as any unfavorable/unintended change in the structure/function/chemistry of the body temporally associated with the use of study drug, or any worsening of a preexisting condition.
A serious AE (SAE) was any AE that resulted in death, was life threatening, resulted in a persistent or significant disability/incapacity, resulted in or prolonged an existing inpatient hospitalization, was a congenital anomaly/birth defect, was a new cancer, or was an overdose.
Measured: Day 1 up to disease progression, toxicity, or death, assessed up to 30 days after end of treatment (up to 30 months)
Laboratory AE Summary
An AE was defined as any unfavorable/unintended change in the structure/function/chemistry of the body temporally associated with the use of study drug, or any worsening of a preexisting condition.
A SAE was any AE that resulted in death, was life threatening, resulted in a persistent or significant disability/incapacity, resulted in or prolonged an existing inpatient hospitalization, was a congenital anomaly/birth defect, was a new cancer, or was an overdose.
A lab (S)AE was any lab value considered clinically significant in the investigator's judgment.
Measured: Day 1 up to disease progression, toxicity, or death, assessed up to 29 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Sep 2005May 2011

First posted26 May 2005 (estimated)
Study startSep 2005
Primary completionDec 2009
Study completionMay 2011

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Multiple MyelomaStudies of the same condition, open and under way.
More trials run by Merck Sharp & Dohme LLCThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 34 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00111813
Sponsor's protocol ID: 0683-015
Other IDs: 2005_018
Status last verified: May 2015
First submitted: 25 May 2005
Last updated: 21 May 2015
Results posted: Yes, on ClinicalTrials.gov

Publications

Weber DM, Graef T, Hussein M, Sobecks RM, Schiller GJ, Lupinacci L, Hardwick JS, Jagannath S. Phase I trial of vorinostat combined with bortezomib for the treatment of relapsing and/or refractory multiple myeloma. Clin Lymphoma Myeloma Leuk. 2012 Oct;12(5):319-24. doi: 10.1016/j.clml.2012.07.007.
PubMed 23040438

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

Official record

Not yet recruitingPhase 2
Study of YKST02 in Adults With Relapsed or Refractory Multiple Myeloma
Relapsed or Refractory Multiple Myeloma (RRMM)
RecruitingPhase 2
Engaging T-cells to Eliminate MRD in Newly Diagnosed Myeloma Optimizing Response With Talquetmab and Teclistamab (ROTATE)
Multiple Myeloma
Active, not recruitingPhase 3
A Phase III Study of Eque-cel in Subjects With Len-refractory RRMM (FUMANBA-03)
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Active, not recruitingPhase 1/2
A Window of Opportunity Trial to Learn if Linvoseltamab is Safe and Well Tolerated, and How Well it Works in Adult Participants With Recently Diagnosed Multiple Myeloma Who Have Not Already Received Treatment
Multiple Myeloma
Active, not recruitingPhase 2
Testing AZD5363 as a Potential Targeted Treatment in Cancers With AKT Genetic Changes (MATCH-Subprotocol Y)
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All Multiple Myeloma trials

Study at a glance

From the registry record, last updated by the sponsor on 21 May 2015. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Phase I Clinical Trial of Vorinostat (MK-0683) in Combination With Bortezomib in Patients With Advanced Multiple Myeloma
ClinicalTrials.gov ID: NCT00111813
Acronym / sponsor ID: 0683-015
Conditions: Multiple Myeloma
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 34 participants (actual)
Lead sponsor: Merck Sharp & Dohme LLCIndustry (pharma, biotech, devices)
Study start: Sep 2005
Primary completion: Dec 2009 (actual)
Study completion: May 2011 (actual)
First posted: 26 May 2005 (estimated)
Results: Posted 6 Apr 2011

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

The purposes of this study are:

To determine the maximum tolerated dose (MTD) for the combination of oral vorinostat and bortezomib in participants with advanced multiple myeloma
To assess the safety and tolerability of this regimen and to document the participant's clinical status (by anti-tumor activity) for this combination, as determined per standard of care.

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 6

Arm	Type	Receives
vorinostat 200 mg + bortezomib 0.7 mg/m^2	Experimental	Drug: vorinostat, Drug: bortezomibVorinostat capsules given twice daily (b.i.d.); bortezomib injection given on Days 4, 8, 11, and 15 of each cycle.
vorinostat 200 mg + bortezomib 0.9 mg/m^2	Experimental	Drug: vorinostat, Drug: bortezomibVorinostat capsules given b.i.d.; bortezomib injection given on Days 4, 8, 11, and 15 of each cycle.
vorinostat 300 mg + bortezomib 1.3 mg/m^2	Experimental	Drug: vorinostat, Drug: bortezomibVorinostat given once daily (q.d.); bortezomib given on Days 1, 4, 8, and 11 of each cycle.
vorinostat 400 mg + bortezomib 0.9 mg/m^2	Experimental	Drug: vorinostat, Drug: bortezomibVorinostat given q.d.; bortezomib given on Days 1, 4, 8, and 11 of each cycle.
vorinostat 400 mg + bortezomib 1.1 mg/m^2	Experimental	Drug: vorinostat, Drug: bortezomibVorinostat given q.d.; bortezomib given on Days 1, 4, 8, and 11 of each cycle.
vorinostat 400 mg + bortezomib 1.3 mg/m^2	Experimental	Drug: vorinostat, Drug: bortezomibVorinostat given q.d.; bortezomib given on Days 1, 4, 8, and 11 of each cycle.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (6 listed)

Adults with refractory or relapsed multiple myeloma
Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 (a measurement to determine participant's ability to perform daily activities)
Adequate bone marrow reserve
Adequate hepatic and renal function
Ability to swallow capsules

Key exclusion criteria (5 listed)

Participants who plan to have a bone marrow transplant within 4 weeks of start of treatment
Participants with prior treatment with other investigational agents with a similar anti-tumor mechanism
Participants with other active/uncontrolled clinically significant illness
Pregnant or nursing female participants
Participants who received bortezomib within 3 months of start of this trial

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
vorinostatAlso: MK0683, Zolinza®, Suberoylanilide Hydroxamic Acid (SAHA)Vorinostat capsules. Treatment in 21 day cycles (participants receive vorinostat for 14 days followed by a 7 day break).	Drug	vorinostat 200 mg + bortezomib 0.7 mg/m^2, vorinostat 200 mg + bortezomib 0.9 mg/m^2, vorinostat 300 mg + bortezomib 1.3 mg/m^2, vorinostat 400 mg + bortezomib 0.9 mg/m^2, vorinostat 400 mg + bortezomib 1.1 mg/m^2, vorinostat 400 mg + bortezomib 1.3 mg/m^2
bortezomibAlso: VelcadeBortezomib injection. Given twice weekly for 2 weeks with a 1 week break. Treatment in 21 day cycles.	Drug	vorinostat 200 mg + bortezomib 0.7 mg/m^2, vorinostat 200 mg + bortezomib 0.9 mg/m^2, vorinostat 300 mg + bortezomib 1.3 mg/m^2, vorinostat 400 mg + bortezomib 0.9 mg/m^2, vorinostat 400 mg + bortezomib 1.1 mg/m^2, vorinostat 400 mg + bortezomib 1.3 mg/m^2

Primary outcome

Mean Duration of Treatment With Vorinostat
Time frame: Day 1 to an event causing discontinuation from the study, assessed up to 29 months
Event causing discontinuation from the study was defined as (1) progressive disease OR (2) intolerable toxicity. Progressive disease was defined as: * >25% increase in the level of serum monoclonal paraprotein. * 25% increase in 24-hour urinary light chain excretion. * >25% increase in plasma cells in a bone marrow aspirate or on trephine biopsy. * Development of new bone lesions or soft tissue plasmacytomas. * Development of hypercalcemia. Intolerable toxicity was based on the clinical judgment of the investigator.

4 secondary outcomes

Number of Participants With Dose Modifications of Either Vorinostat or Bortezomib Due to Adverse Experiences (AEs) After Treatment With Study Drug
Time frame: Day 1 to disease progression, toxicity, or death, assessed up to 29 months
Mean Time to First AE Resulting in a Dose Modification in Either Vorinostat or Bortezomib
Time frame: Day 1 to disease progression, toxicity, or death, assessed up to 29 months
Clinical AE Summary
Time frame: Day 1 up to disease progression, toxicity, or death, assessed up to 30 days after end of treatment (up to 30 months)
Laboratory AE Summary
Time frame: Day 1 up to disease progression, toxicity, or death, assessed up to 29 months

Results and safety

Results posted to the registry on 6 Apr 2011, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Vorinostat 200 mg + Bortezomib 0.7 mg/m^2	3	0
Vorinostat 200 mg + Bortezomib 0.9 mg/m^2	3	0
Vorinostat 300 mg + Bortezomib 1.3 mg/m^2	10	0
Vorinostat 400 mg + Bortezomib 0.9 mg/m^2	6	1
Vorinostat 400 mg + Bortezomib 1.1 mg/m^2	6	0
Vorinostat 400 mg + Bortezomib 1.3 mg/m^2	6	0

Primary outcome: Mean Duration of Treatment With Vorinostat

Time frame: Day 1 to an event causing discontinuation from the study, assessed up to 29 months. Mean (Full Range). Unit: Days

Measure	All Participants n = 34
200 mg	4.6 (1 to 15)
300 mg	72.6 (28 to 210)
400 mg	107.1 (11 to 496)

4 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Vorinostat 200 mg + Bortezomib 0.7 mg/m^2	0 of 3 (0%)	3 of 3 (100%)	Not reported
Vorinostat 200 mg + Bortezomib 0.9 mg/m^2	1 of 3 (33.3%)	3 of 3 (100%)	Not reported
Vorinostat 300 mg + Bortezomib 1.3 mg/m^2	2 of 10 (20%)	10 of 10 (100%)	Not reported
Vorinostat 400 mg + Bortezomib 0.9 mg/m^2	4 of 6 (66.7%)	6 of 6 (100%)	Not reported
Vorinostat 400 mg + Bortezomib 1.1 mg/m^2	4 of 6 (66.7%)	6 of 6 (100%)	Not reported
Vorinostat 400 mg + Bortezomib 1.3 mg/m^2	2 of 6 (33.3%)	6 of 6 (100%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 21 May 2015.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 23040438Weber DM, Graef T, Hussein M, Sobecks RM, Schiller GJ, Lupinacci L, Hardwick JS, Jagannath S. Phase I trial of vorinostat combined with bortezomib for the treatment of relapsing and/or refractory multiple myeloma. Clin Lymphoma Myeloma Leuk. 2012 Oct;12(5):319-24. doi: 10.1016/j.clml.2012.07.007.

Related trials for Multiple Myeloma

Not yet recruitingPhase 2
Study of YKST02 in Adults With Relapsed or Refractory Multiple Myeloma
Relapsed or Refractory Multiple Myeloma (RRMM)
RecruitingPhase 2
Engaging T-cells to Eliminate MRD in Newly Diagnosed Myeloma Optimizing Response With Talquetmab and Teclistamab (ROTATE)
Multiple Myeloma
Active, not recruitingPhase 3
A Phase III Study of Eque-cel in Subjects With Len-refractory RRMM (FUMANBA-03)
Multiple Myeloma
Active, not recruitingPhase 1/2
A Window of Opportunity Trial to Learn if Linvoseltamab is Safe and Well Tolerated, and How Well it Works in Adult Participants With Recently Diagnosed Multiple Myeloma Who Have Not Already Received Treatment
Multiple Myeloma
Active, not recruitingPhase 2
Testing AZD5363 as a Potential Targeted Treatment in Cancers With AKT Genetic Changes (MATCH-Subprotocol Y)
Advanced Lymphoma, Advanced Malignant Solid Neoplasm

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Medical Monitor study director

Merck Sharp & Dohme LLC

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing vorinostat and bortezomib in people with Multiple Myeloma, run by Merck Sharp & Dohme LLC.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 21 May 2015. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 6 Apr 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Mean Duration of Treatment With Vorinostat (time frame: Day 1 to an event causing discontinuation from the study, assessed up to 29 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00111813, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 May 2015.